Immunogenic cell death (ICD) is a form of cell death characterized by the release of danger signals required to trigger an adaptive immune response against
tumor-associated
antigens.
Silver nanoparticles (AgNP) display anti-proliferative and cytotoxic effects in
tumor cells, but it has not been previously studied whether AgNP act as an ICD inductor. The present study evaluated the in vitro release of
calreticulin as a damage-associated molecular pattern (DAMP) associated with the cytotoxicity of AgNP and their in vivo anti-
cancer effects. In vitro, mouse CT26 colon
carcinoma and MCA205
fibrosarcoma cells were exposed to AgNP and then cell proliferation, adhesion, and release of
calreticulin were determined. The results indicated there were time- and concentration-related anti-proliferative effects of AgNP in both the CT26 and MCA205 lines. Concurrently, changes in cell adhesion were detected mainly in the CT26 cells. Regarding DAMP detection, a significant increase in
calreticulin was observed only in CT26 cells treated with
doxorubicin and AgNP; however, no differences were found in the MCA205 cells. In vivo, the survival and growth of subcutaneous
tumors were monitored after vaccination of mice with cell debris from
tumor cells treated with AgNP or after intra-tumoral administration of AgNP to established
tumors. Consequently, anti-tumoral prophylactic immunization with AgNP-dead cells failed to protect mice from
tumor re-challenge; intra-
tumor injection of AgNP did not induce a significant effect. In conclusion, there was a noticeable anti-tumoral effect of AgNP in vitro in both CT26 and MCA205 cell lines, accompanied by the release of
calreticulin in CT26 cells. In vivo, immunization with cell debris derived from AgNP-treated
tumor cells failed to induce a protective immune response in the
cancer model mice. Clearly, further research is needed to determine if one could combine AgNP with other ICD inducers to improve the anti-
tumor effect of these nanoparticles in vivo.